In the context of Chinese narrative medicine， narrative foreclosure is an abnormal state in the process of life narrative， which is the “fractured or stagnation of the life narrative process”. Based on analyzing the characteristics and performance of typical traumatic narrative foreclosures in literary works and clinical reality， this paper proposed that narrative care is of great significance for the traumatic subject to get out of narrative foreclosures and re-enter the narrative process of mental and physical comfort. “Narrative care” is a way of care in which medical staff or educator in health institutions use their narrative capital and narrative wisdom to establish interpersonal narrative connections with themselves， their families， and service or education recipients， so as to nourish subjects in narrative foreclosure and help them get out of life’s dilemmas. Narrative caregivers assist the traumatic subjects in gaining the restorative power to repair the fractured narrative process of life through the construction of a narrative community， getting out of isolation， achieving growth， and restoring overall health.

OBJECTIVE: In this study, the role and potential mechanism of transformer 2β (Tra2β) in cervical cancer were explored. METHODS: The transcriptional data of Tra2β in patients with cervical cancer from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases were investigated. The functions of Tra2β were evaluated by using Western blot, MTT, colony formation, Transwell assays, and nude mouse tumor formation experiments. Target genes regulated by Tra2β were studied by RNA-seq. Subsequently, representative genes were selected for RT-qPCR, confocal immunofluorescence, Western blot, and rescue experiments to verify their regulatory relationship. RESULTS: The dysregulation of Tra2β in cervical cancer samples was observed. Tra2β overexpression in Siha and Hela cells enhanced cell viability and proliferation, whereas Tra2β knockdown showed the opposite effect. Alteration of Tra2β expression did not affect cell migration and invasion. Furthermore, tumor xenograft models verified that Tra2β promoted cervical cancer growth. Mechanically, Tra2β positively regulated the mRNA and protein level of SP1, which was critical for the proliferative capability of Tra2β. CONCLUSION This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo, which provides a comprehensive understanding of the pathogenesis of cervical cancer.
Humans ; Animals ; Mice ; Female ; Uterine Cervical Neoplasms/genetics* ; HeLa Cells ; Cell Proliferation ; Biological Assay ; Transcription Factors ; Sp1 Transcription Factor/genetics*

OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.

OBJECTIVE To evaluate the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from the Cochrane Library， Medline， Embase， CINAHL， Web of Science， ProQuest， Google Scholar， CNKI， Wanfang Data， Baidu academic database， World Health Organization International Clinical Trials Registration Platform and ClinicalTrials. gov， randomized controlled trials （RCTs） about intravenous immunoglobulin （IVIG）+glucocorticoid or cyclosporine or tumor necrosis factor-alpha （TNF-α） blocker （trial group） versus standard IVIG therapy （control group） were collected from the establishment of the database to Feb. 28th， 2023. After screening the literature， extracting data， and evaluating the quality of the literature， Stata 14.2 software was used for network meta-analysis. RESULTS Ten RCTs with a total of 1 323 participants involving six measures were included： standard IVIG therapy， glucocorticoid therapy，cyclosporine therapy， TNF- α blocker therapy， remedial glucocorticoid therapy and remedial TNF- α blocker therapy. Results of network meta-analysis showed that the incidence of coronary artery aneurysms （CAA） at 4-8 weeks was significantly lower in patients receiving glucocorticoid therapy than receiving standard IVIG therapy and TNF-α blocker therapy. The incidences of CAA at 4-8 weeks in children treated with remedial glucocorticoid therapy and remedial TNF- α blocker therapy were significantly higher than those treated with glucocorticoid therapy； there was no significant difference in the incidence of CAA at 4-8 weeks among other interventions （P＞ 0.05）； network meta-order of the incidence was glucocorticoid therapy＜cyclosporine therapy＜standard IVIG therapy＜remedial TNF-α blocker therapy＜remedial glucocorticoid therapy＜TNF-α blocker therapy. The incidence of initial IVIG resistance in children receiving cyclosporine therapy was significantly lower than those receiving standard IVIG therapy； there was no significant difference in the incidence of initial IVIG resistance among other interventions （P＞0.05）； network meta-order of the incidence was cyclosporine therapy＜glucocorticoid therapy＜TNF-α blocker therapy＜standard IVIG therapy. There was no significant difference in the incidence of ADR among different interventions （P＞0.05）； network meta-order of the incidence was remedial TNF-α blocker therapy＜TNF-α blocker therapy＜standard IVIG therapy＜glucocorticoid therapy＜cyclosporine therapy. CONCLUSIONS Glucocorticoid therapy at the initial treatment can significantly reduce the risk of CAA at 4-8 weeks in children with Kawasaki disease； cyclosporine has a significant effect on improving initial IVIG resistance， and the use of TNF-α blocker in the remedial stage may have the lowest incidence of adverse reactions.

Humans ; Stomach Neoplasms/pathology* ; Gastric Mucosa/pathology* ; Adenocarcinoma/pathology*

In this study, we investigated the pharmacological effect and possible molecular mechanism of higenamine (HG) in isoproterenol (ISO)-induced myocardial infarction (MI). All procedures were approved by the Institutional Animal Care and Use Committee of the Guangzhou University of Chinese Medicine. ISO was used to induce MI model in rats and H9c2 cells. The effects of HG on biomarkers and cardiac function in MI rats were evaluated by enzyme linked immunosorbent assay (ELISA), echocardiography and hematoxylin-eosin staining (HE). The expression of apoptosis and autophagy related proteins were detected by Western blot in myocardial tissue and H9c2 cells, as well as methyltransferase-like 3 (METTL3) and transcription factor EB (TFEB) protein expression. Molecular docking was used to evaluate the interaction between HG and METTL3. The results showed that HG significantly improved cardiac function and pathologic changes in ISO-induced MI, and inhibited the levels of MI-related biomarkers such as creatine kinase Mb (CK-MB), creatine kinase (CK) and lactate dehydrogenase (LDH). Mechanism studies showed that HG inhibited the expression of apoptosis-related proteins (Bax/Bcl2, caspase3, cleaved-caspase3). Interestingly, HG up-regulated the expression of autophagy related protein Beclin1, promoted autophagy flux, and decreased the ratio of light chain 3B-I/light chain 3B-II (LC-3B-I/LC-3B-II). Further studies found that HG increased the autophagy regulator TFEB and inhibited METTL3 expression. Molecular docking results showed that HG had a good interaction with METTL3. Taken together, HG has a potential anti-MI effect via regulating METTL3/TFEB signaling pathway-mediated autophagy.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals ; Apoptosis ; Boron/toxicity* ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Trichloroacetic Acid/toxicity* ; Tumor Suppressor Protein p53/metabolism*

Objective: The underlying mechanism of Ezrin in ovarian cancer (OVCA) is far from being understood. Therefore, this study aimed to assess the role of Ezrin in OVCA cells (SKOV3 and CaOV3) and investigate the associated molecular mechanisms. Methods: We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, RhoA and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells. Results: The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of RhoA rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation. Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.
Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cytoskeletal Proteins/metabolism* ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Ovarian Neoplasms/pathology* ; Stress Fibers/metabolism* ; rhoA GTP-Binding Protein/metabolism*

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Acute-On-Chronic Liver Failure ; Humans ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies

【Objective】To screen survival-related differential expression of long non-coding RNA（lncRNA）and its co-expressed genes in breast cancer patients and to verify their expression in breast cancer cells.【Methods】RNA-seq data of 943 cases（837 breast cancer + 106 normal controls）by the TCGA database were screened，and found that long non-coding MAPT-AS1 highly expressed，and breast cancer patients had longer survival. The long non-coding MAPT- AS1 overexpression and interference plasmid was constructed，and the constructed plasmid was transfected into breast cancer cell line T47D，and the stably expressed T47D cell line was screened by puromycin. The expression of long non-coding MAPT-AS1 and its co-expressed genes was verified by the methods of RT-qPCR.【Results】Fluorescence microscopy and RT-qPCR confirmed that the long non-coding MAPT-AS1 overexpression and interference-transfected breast cancer cell line T47D were successfully constructed，and the long non-coding MATS-AS1 interference fragment shRNA3 with the highest interference efficiency was screened. The expression of MAPT ，MAPT- IT1 and NXNL2 in the co-expressed gene was decreased after transfection of the shRNA3 interference fragment ，which was consistent with the expression trend of the long non-coding MAPT-AS1.【Conclusion】The long non-coding MAPT-AS1 overexpression and interference plasmid transfected breast cancer cell line T47D were successfully constructed，and the expression of the co- expressed gene was consistent with the database. The study laid the foundation for further study of the mechanism of action of long non-coding MAPT-AS1 gene in breast cancer.